Organochlorines such as the DDT metabolite DDE and polychlorinated biphenyls (PCBs) are persistent organic pollutants that may be toxic at levels encountered by the general population, through exposure in the food chain. PCBs interfere with neurodevelopment in animal experiments but human results are mixed. Each organochlorine has several types of biologic activity, so potential mechanisms of action are a challenge to pin down. For example, DDE interferes with androgen binding to its receptor, and it may also interfere with closing of sodium channels in cell membranes. Most of my work in this area is based on analysis of serum from pregnant women who were in a cohort study named the Collaborative Perinatal Project (CPP). Here I describe some of my results from the CPP study (not all is published yet). Results from other studies I have done on the health effects of persistent organic pollutants are indicated in the list of publications. Sera from over 50,000 pregnant women in the CPP have been frozen at -20 degrees Centigrade since 1959-1965, and with the health data on their offspring constitute a resource that is still actively used by many investigators. We selected a subset of about 2,800 children born in 1959-1966 and determined organochlorine concentrations in the corresponding stored maternal pregnancy sera. We have examined DDE levels in relation to fetal loss in previous pregnancies, and, in the CPP pregnancy, preterm birth, small-for-gestational-age, and birthweight; in all cases we found associations suggestive of adverse effects. To look for evidence of androgen-blocking, we examined maternal DDE level during pregnancy in relation to adjusted odds of cryptorchidism, hypospadias, and polythelia [extra nipples] among their male offspring; for these outcomes the results were suggestive but equivocal. We evaluated prenatal PCB exposure in relation to developmental assessment performance at 8 months of age, cognitive test scores (IQ) on the Wechsler Intelligence Scale for Children (WISC) at age 7 years, and hearing as reflected by audiometric examination at age 8 years. None of these studies showed any associations. Our dataset is very rich and we will continue to publish results based on the CPP for years to come. If we detect health effects of low-level exposure to organochlorine compounds, this will have several implications. First, if we see effects at levels encountered by the U.S. population at present, we will need to develop techniques to reduce intake or body burdens. A recent Institute of Medicine report suggested reduction of dioxin exposure in women of reproductive age, so this is not just a theoretical consideration. Second, we will need to decrease the production and use of persistent organochlorine compounds, especially DDT in developing countries (most other persistent organic pollutants have been banned in the United States and other developed countries). The decision to phase out DDT use for malaria control will depend heavily on data on adverse effects of DDT as compared with the alternative agents available for vector control. Last year's progress Because this project is now in the data analysis and reporting phase, the progress is reflected by the publications. Briefly, in the past year, we have reported on PCBs and neurodevelopment (no association in our data), and DDE and fetal loss (association found).